Study of ONO-4538 in Non-Squamous Non-Small Cell Lung Cancer (TASUKI-52)

Phase 3

Completed

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: ONO-4538; Drug: Carboplatin; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Placebo

• Registration Number: NCT03117049
• Lead Sponsor: Ono Pharmaceutical Co. Ltd

Brief Summary

The purpose of study is to compare the efficacy and safety of ONO-4538 in combination with carboplatin, paclitaxel, and bevacizumab (ONO-4538 group) to placebo in combination with carboplatin, paclitaxel, and bevacizumab (placebo group) in chemotherapy-naïve subjects with stage IIIB/IV or recurrent non-squamous non-small cell lung cancer unsuitable for radical radiation in a multicenter, randomized, double-blind study.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-12
• Study First Submitted QC: 2017-04-14
• Study First Posted: 2017-04-17
• Study Start: 2017-06-13
• Primary Completion: 2020-02-10
• Results First Submitted: 2021-10-21
• Results First Submitted QC: 2022-04-25
• Results First Posted: 2022-04-26
• Study Completion: 2023-12-04
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-02
• Last Update Posted: 2024-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

• Subjects with histologically- or cytologically-confirmed non-squamous non-small cell lung cancer
• Subjects who received a diagnosis of stage IIIB/IV or recurrent non-squamous non-small cell lung cancer unsuitable for radical radiation according to the UICC-TNM Classification (7th edition) with no prior systemic anticancer therapy
• Subjects with at least one measurable lesion by radiographic tumor assessments per RECIST 1.1 criteria
• Subjects who are able to provide tumor tissue specimens.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1

Exclusion Criteria

• Subjects with known EGFR mutations, including deletions in exon 19 and exon 21 (L858R) substitution mutations.
• Subjects with known ALK translocations.
• Complication or history of severe hypersensitivity reactions to antibody products or platinum-containing compounds
• Subjects with autoimmune disease or known chronic or recurrent autoimmune disease.
• Subjects with multiple cancer.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ONO-4538 group	ONO-4538	ONO-4538: 360 mg solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
Placebo group	Bevacizumab	Placebo: Placebo solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
Placebo group	Placebo	Placebo: Placebo solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
ONO-4538 group	Carboplatin	ONO-4538: 360 mg solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
ONO-4538 group	Paclitaxel	ONO-4538: 360 mg solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
ONO-4538 group	Bevacizumab	ONO-4538: 360 mg solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
Placebo group	Carboplatin	Placebo: Placebo solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
Placebo group	Paclitaxel	Placebo: Placebo solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) as Assessed by the Independent Radiology Review Committee (IRRC)	Approximately 32 months	PFS (as assessed by the IRRC) will be calculated using the following formula : PFS (days) = "date when overall response is assessed as progressive disease (PD) or date of death (for any reason), whichever comes first" - "date of randomization" + 1. Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Approximately 32 months
Best Overall Response (BOR [as Assessed by the IRRC])	Approximately 32 months
Disease Control Rate (DCR [as Assessed by the IRRC])	Approximately 32 months	DCR represents the proportion of subjects whose best overall response was assessed as CR, PR, or stable disease (SD). Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria.
Objective Response Rate (ORR [as Assessed by the IRRC])	Approximately 32 months	ORR represents the proportion of subjects whose best overall response was assessed as complete response (CR) or partial response (PR). Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria.
Duration of Response (DOR [as Assessed by the IRRC])	Approximately 32 months	The lower and upper limits of 95% CI for the median are censored value in the both groups.

Trial Locations

Locations (84)

Aichi Clinical Site2; 🇯🇵 Nagoya, Aichi, Japan

Aichi Clinical Site3; 🇯🇵 Nagoya, Aichi, Japan

Aichi Clinical Site4; 🇯🇵 Nagoya, Aichi, Japan

Aichi Clinical Site; 🇯🇵 Toyoake, Aichi, Japan

Aomori Clinical Site2; 🇯🇵 Hirosaki, Aomori, Japan

Aomori Clinical Site; 🇯🇵 Hirosaki, Aomori, Japan

Chiba Clinical Site; 🇯🇵 Chiba, Japan

Ehime Clinical Site; 🇯🇵 Matsuyama, Ehime, Japan

Fukuoka Clinical Site; 🇯🇵 Fukuoka, Japan

Fukushima Clinical Site; 🇯🇵 Kōriyama, Fukushima, Japan

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